Connective tissue macromolecules are important components in maintaining the integrity of lung structures. The carbohydrate-protein macromolecules, proteoglycans are of specific interest and variations in the composition of these macromolecules are noted at different sites of the lung, for example, gas-exchange tissue, pleura and bronchiolar structures. The major proteoglycan in the gas-exchange tissue and in the pleura is a heparan sulfate proteoglycan. The bronchioles are composed of a chondroitin sulfate proteoglycan. Other proteoglycans, although present in lesser amounts, may have important biologic functions. This research will explore the nature of various proteoglycans from different sites of bovine lung and will study their potential in biologic functions. Glycosaminoglycans (GAG), linkage region and core protein of the proteoglycans will be characterized. Proteoglycan-hyaluronate aggregates will be isolated from bovine lung and the nature of the aggregates will be studied. Interactions of proteoglycans with fibrous structures of the lung will be investigated. These interactions may be of importance in producing an insoluble matrix which performs a protective function by excluding potentially destructive molecules such as proteases. As models of human diseases experimental emphysema and pulmonary hypertension are of primary interest. The major objective of the research program is to define more precisely the chemistry and function of proteoglycans in normal lung and the role these compounds play in the pathogenesis of lung disease, emphysema and pulmonary hypertension.